Molecularly Imprinted Polymer Microspheres Research Articles

Fabrication of Atrazine Molecularly Imprinted Polymer Microsphere by Two Step Seed Swelling Polymerization Method

AbstractAtrazine molecularly imprinted polymer microspheres (MIPMs) were fabricated by two step seed swelling polymerization method, using atrazine as a template molecule, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EDMA) as a crosslinking agent and toluene/dodecanol as a porogenic agent and a series of MIPMs with even particle size of 3‐5 μm and good dispersivity could be obtained under the optimal condition. Equilibrium binding experiments were comparably studied about the binding capacity of the resulted polymers. We packed the polymers into empty chromatographic steel tube columns (2.1 mm I.D. × 10 cm) to prepare liquid chromatographic columns used for the evaluation of specificity with similar structure compounds. The proposed method has been successfully applied to the determination of limited atrazine in water samples. The results showed that a good linear relationship of atrazine was maintained within 0.1‐20 mg/L (r = 0.9992), the sample recovery was in a range of 92.1‐102.0%, with a RSD lower than 5% (n = 6) and a detection limit of 0.041 mg/L.

Azobenzene-Containing Molecularly Imprinted Polymer Microspheres with Photo- and Thermoresponsive Template Binding Properties in Pure Aqueous Media by Atom Transfer Radical Polymerization

A facile, general, and highly efficient approach to obtain azobenzene (azo)-containing molecularly imprinted polymer (MIP) microspheres with both photo- and thermoresponsive template binding properties in pure aqueous media is described for the first time, which involves the first synthesis of "living" azo-containing MIP microspheres with surface-immobilized alkyl halide groups via atom transfer radical precipitation polymerization (ATRPP) and their subsequent modification via surface-initiated atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAm). The successful grafting of poly(NIPAAm) (PNIPAAm) brushes onto the obtained MIP microspheres was confirmed by FT-IR, SEM, water dispersion stability and static contact angle studies, and template binding experiments. The introduction of PNIPAAm brushes onto the azo-containing MIP microspheres significantly improved their surface hydrophilicity and imparted thermoresponsive properties to them, leading to their pure water-compatible and thermoresponsive template binding properties. In addition, the binding affinity of the imprinted sites in the grafted azo-containing MIP microspheres was found to be photoresponsive toward the template in pure water, and this photoregulation process proved to be highly repeatable under photoswitching conditions.

Synthesis and evaluation of uniformly sized carbamazepine‐imprinted microspheres and nanospheres prepared with different mole ratios of methacrylic acid to methyl methacrylate for analytical and biomedical applications

AbstractIn this work, we initiated to study new synthetic conditions to obtain uniformly sized molecularly imprinted polymers (MIPs) in the micrometer to nanometer range, using carbamazepine (CBZ) as a model template. The MIPs were successfully prepared by precipitation polymerization using methacrylic acid (MAA) and methyl methacrylate (MMA) as functional monomers at different mole ratios. The effect of MAA‐to‐MMA mole ratios on the morphology, binding, recognition, and release behaviors of the final particles were studied, and the adjusting possibility of these properties was also obtained. The produced polymers were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry, and their morphology was precisely examined by scanning electron microscopy and photon correlation spectroscopy. We obtained very uniform imprinted nanospheres and microspheres with diameter in the range of 120 nm to 1.74 μm under various conditions. Among the MIP nanospheres and microspheres prepared, the MIPs using MAA‐to‐MMA mole ratio of 1 : 2 showed nanospheres with the lower polydispersity index (0.004) and the highest selectivity factor (10.4), which is defined as the binding ratio of CBZ and oxcarbazepine as template analog. Results from binding experiments proved that MIPs exhibit specific affinity to CBZ in contrast to control polymers, and this performance was affected by pH and concentration of the loading solution. Moreover, release experiments showed the controlled release of CBZ in long‐time period. The 50% of loaded CBZ was released from the imprinted nanospheres within the first 30 h, whereas another 50% was released in the following 160 h. The release kinetics of CBZ from the MIPs highly affected with the properties of particles. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Imprinted polymer beads enabling direct and selective molecular separation in water

In this paper, we describe the synthesis of water-compatible Molecularly Imprinted Polymer (MIP) microspheres by nanoparticle-stabilized emulsion (Pickering emulsion) polymerization. During the polymerization, the amount of the porogen used not only affected the stability of the Pickering emulsion but also the specific molecular recognition of the obtained MIP microspheres. Under optimized conditions, the MIP microspheres synthesized had a porous and hydrophilic surface. Scanning electron microscopy and fluorescent labeling experiments indicated that the MIP microspheres had particle sizes of 165 ± 38 μm. Selective molecular recognition with the MIP microspheres was studied through equilibrium binding analysis and liquid chromatography experiments under pure aqueous conditions. Using the new MIP microspheres as solid phase extraction (SPE) absorbents, low concentration organic pollutants (β-blockers) were effectively enriched from tap water and easily detected using HPLC-MS analysis.

Preparation of MIP Microspheres by Precipitation Polymerization with 1-Phenyl-1-Propanol as Template

Molecular imprinting polymer microspheres were prepared by precipitation polymerization with methacrylic acid as functional monomer and 1-phenyl-1-propanol as template. The effects of synthesis conditions, including the kind of solvent, polymerization temperature, the concentration of template and initiator, rotational speed and pre-polymerization time, on the characteristics of the molecularly imprinted polymer microspheres were studied. The rebinding experiments showed that the molecularly imprinted polymer microspheres synthesized by precipitation polymerization at 60°C, with acetonitrile as solvent and the concentrations of both template and initiator of 0.01mol L-1, have good specific recognition and higher affinity capacity.

Efficient One‐Pot Synthesis of Water‐Compatible Molecularly Imprinted Polymer Microspheres by Facile RAFT Precipitation Polymerization

Molecular imprinting is a versatile and straightforward method for the preparation of polymer receptors with tailor-made recognition sites. Despite the tremendous progress made in this field, many challenges still remain to be addressed. In particular, it has been shown that the presently developed molecularly imprinted polymers (MIPs) are normally only organic solvent compatible and they mostly fail to show specific template bindings in pure aqueous solutions, thus significantly limiting their practical applications in the field of biotechnology. Although some approaches, which either use specifically designed functional monomers or apply the conventional imprinting protocol, have been developed for the preparation of MIPs with molecular recognition ability under aqueous conditions, versatile approaches for the preparation of MIPs that are applicable in pure aqueous environments are still rare. Herein, we report a new and efficient one-pot approach to obtain pure-water-compatible and narrowly dispersed MIP microspheres with surface-grafted hydrophilic polymer brushes by facile reversible addition/fragmentation chaintransfer (RAFT) precipitation polymerization (RAFTPP), mediated by hydrophilic macromolecular chain-transfer agents (Macro-CTAs; Scheme 1). The presence of hydrophilic polymer brushes on MIP microspheres significantly improved their surface hydrophilicity and dramatically reduced their hydrophobic interactions with template molecules in pure aqueous media, thus leading to their water compatibility. The easy availability of many different hydrophilic Macro-CTAs (by either RAFT polymerization of hydrophilic monomers or hydrophilic polymer end group modification), together with the versatility of RAFTPP for the controlled preparation of MIP microspheres, makes this strategy highly applicable for the design of hydrophilic and water-compatible MIPs. Two strategies have been developed for the synthesis of water-compatibleMIPs by improving their surface hydrophilicity; these strategies involve the use of a hydrophilic comonomer, functional monomer, or crosslinker in the molecular imprinting process, and the postmodification of the preformed MIPs. Although simple in principle, the former strategy either requires time-consuming optimization of MIP formulation components or can only be applied in some special systems. In comparison, the latter strategy, which involves the surface grafting of hydrophilic polymer layers, has proven highly attractive because it not only significantly improves the MIPs surface hydrophilicity, but also provides a protective layer to prevent protein molecules from blocking their imprinting sites in biological solutions. Very recently, we have successfully prepared pure-water-compatible MIP microspheres by the controlled grafting of hydrophilic polymer layers onto the preformed MIP particles. Compared with this two-step approach, the new strategy presented herein allows the more efficient controlled synthesis of pure-water-compatible MIP microspheres with surface-grafted hydrophilic polymer brushes by a one-pot RAFTPP method. To show proof-of-principle for our strategy, a model noncovalent molecular imprinting system was chosen because Scheme 1. Chemical structures of the utilized RAFT agents (including hydrophilic Macro-CTAs and CDB) and the schematic protocol for the one-pot preparation of water-compatible MIP microspheres by RAFT precipitation polymerization.

Preparation and Characterization of Molecularly Imprinted Polymer Microspheres of p-Nitroaniline

Polystyrene microspheres were prepared by the emulsifier-free polymerization method. Using the polystyrene microspheres as seeds, p-nitroaniline as template molecules, the monodispersed molecularly imprinted polymer microspheres (MIPMs) were prepared by a single-step swelling and polymerization method. The monodispersed molecular imprinted polymers with porous structure were characterized by SEM, and UV-visible spectrophotometry. The adsorption performance of MIPMs for p-nitroaniline was investigated.

Membranes for Specific Adsorption: Immobilizing Molecularly Imprinted Polymer Microspheres using Electrospun Nanofibers

Molecularly imprinted polymer microspheres were immobilized within a polymer nanofiber membrane by electrospinning. Such membranes simplify the handling of functional microspheres and provide specific recognition capabilities for solid-phase extraction and filtration applications. In this study, microspheres were prepared by precipitation polymerization of methacrylic acid and divinylbenzene as a cross-linker with the target molecule (-)-cinchonidine and then, they were electrospun into a non-woven polyacrylonitrile nanofiber membrane. The composite membrane showed specific affinity for (-)-cinchonidine which was attributed to the functional microspheres as confirmed by Raman microscopy. The target molecule capturing capacity of the composite membrane was 5 mg/g or 25 mg/g immobilized functional microsphere. No difference in target affinity was observed between the immobilized microspheres and the free microspheres. These results reveal that electrospun composite membranes are a feasible approach to immobilizing functional microspheres.

Controlled synthesis of water-compatible molecularly imprinted polymer microspheres with ultrathin hydrophilic polymer shells via surface-initiated reversible addition-fragmentation chain transfer polymerization

The first controlled synthesis of pure water-compatible molecularly imprinted polymer (MIP) microspheres with ultrathin hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) shells (including both PHEMA brushes and lightly crosslinked PHEMA hydrogel layer) via surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization is described. The presence of ultrathin hydrophilic polymer shells on the MIP microspheres was confirmed by SEM, FT-IR, fluorescent labeling treatment, contact angle studies, and water dispersion stability test, and some quantitative information including the thickness of the grafted hydrophilic polymer layers as well as the molecular weights and polydispersities of the grafted polymer brushes and their grafting densities was provided. The facile surface-grafting of both PHEMA brushes and PHEMA hydrogel layer on the MIP microspheres proved to be highly efficient for improving their surface hydrophilicity and suppressing the hydrophobically driven nonspecific interactions between the MIPs and template molecules, leading to MIPs with pure water-compatible binding properties. The findings presented here not only prove the general applicability of the controlled hydrophilic polymer brushes-grafting approach in obtaining pure water-compatible MIPs, but also largely extend the scope of this versatile surface-grafting approach through the controlled surface-grafting of hydrophilic polymer hydrogel layer onto the MIPs. Moreover, the significant effect of the chain length of the grafted polymer brushes and the presence of crosslinking in the grafted polymer shells on the surface hydrophilicity and water-compatibility of the MIP microspheres was also demonstrated for the first time, which is of great importance for the rational design of water-compatible MIPs by using this controlled surface-grafting approach.

Development and characterization of molecularly imprinted polymer microspheres for the selective detection of in traditional Chinese medicines.

In the present work, microwave heating was applied to the preparation of kaempferol molecularly imprinted polymer (MIP) microspheres, resulting in much shorter polymerization times. The MIP microspheres were demonstrated with a narrow diameter distribution of 6-9 μm and a spherical shape. The average diameter of 50 microspheres was 8 μm. The results of the morphology observation, the static adsorption performance and the selectivity performance of the MIP microspheres were all superior to that of the MIPs prepared by conventional heating. The imprinting efficiency of the MIP microspheres was 5.0 and 4.2, which were prepared by microwave heating and conventional heating respectively. MIPs prepared by microwave heating were used as sorbent for solid phase extraction and the elution efficiency of kaempferol was 93.1%. The MIPs coupled with solid phase extraction were used for the extraction of kaempferol from Portulaca oleracea L. and Alpinia officinarum. The regression equation was A = -76437.921 + 1.619 × 107C with correlation coefficients of R = 0.9997. The linearity range was 4.5-200 mg L-1 and the limit of detection was 8.0 μg g-1. The recoveries were 90.2% and 88.0% and the RSDs were 1.21% and 1.18% respectively. The results indicated that the proposed MIPs can be favorably used for the extraction of kaempferol in traditional Chinese medicines.

Azobenzene-containing molecularly imprinted polymer microspheres with photoresponsive template binding properties

The first successful preparation of azobenzene (azo)-containing molecularly imprinted polymer (MIP) microspheres with photoresponsive template binding properties is described. A methacrylate azo functional monomer with a pyridine group was used for this purpose, and its good solubility in acetonitrile allowed the implementation of molecular imprinting viaprecipitation polymerization, leading to azo-containing MIP microspheres (number-average diameter = 1.33 μm, polydispersity index = 1.15) with obvious molecular imprinting effects towards the template 2,4-dichlorophenoxyacetic acid (2,4-D), rather fast template rebinding kinetics, and appreciable selectivity over structurally related compounds. The binding association constant Ka and apparent maximum number Nmax for high-affinity sites of the imprinted polymer in the dark environment were determined by Scatchard analysis to be 2.3 × 104 M−1 and 10.0 μmol g−1, respectively. Most importantly, the binding affinity of the imprinted sites in azo-containing MIP microspheres was found to be photoresponsive towards the template, which decreased upon UV light irradiation (as revealed by the resulting lower Ka value for high-affinity sites and reduced specific bindings), whereas it could be recovered during the subsequent thermal (or visible light-induced) back-isomerization. Furthermore, this photoregulation process proved to be highly repeatable under photoswitching conditions.

An efficient approach to obtaining water-compatible and stimuli-responsive molecularly imprinted polymers by the facile surface-grafting of functional polymer brushes via RAFT polymerization

A new and efficient approach to obtaining molecularly imprinted polymers (MIPs) with both pure water-compatible (i.e., applicable in the pure aqueous environments) and stimuli-responsive binding properties is described, whose proof-of-principle is demonstrated by the facile modification of the preformed MIP microspheres via surface-initiated reversible addition–fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAAm). The presence of poly(NIPAAm) (PNIPAAm) brushes on the obtained MIP microspheres was confirmed by FT-IR as well as the water dispersion and static contact angle experiments, and some quantitative information including the molecular weights and polydispersities of the grafted polymer brushes, the thickness of the polymer brush layers, and their grafting densities was provided. In addition, the binding properties of the ungrafted and grafted MIPs/NIPs in both methanol/water (4/1, v/v) and pure water solutions were also investigated. The introduction of PNIPAAm brushes onto the MIP microspheres has proven to significantly improve their surface hydrophilicity and impart stimuli-responsive properties to them, leading to their pure water-compatible and thermo-responsive binding properties. The application of the facile surface-grafting approach, together with the versatility of RAFT polymerization and the availability of many different functional monomers, makes the present methodology a general and promising way to prepare water-compatible and stimuli-responsive MIPs for a wide range of templates.

One‐pot synthesis of surface‐functionalized molecularly imprinted polymer microspheres by iniferter‐induced “living” radical precipitation polymerization

AbstractThis article describes for the first time the development of a new polymerization technique by introducing iniferter‐induced “living” radical polymerization mechanism into precipitation polymerization and its application in the molecular imprinting field. The resulting iniferter‐induced “living” radical precipitation polymerization (ILRPP) has proven to be an effective approach for generating not only narrow disperse poly(ethylene glycol dimethacrylate) microspheres but also molecularly imprinted polymer (MIP) microspheres with obvious molecular imprinting effects towards the template (a herbicide 2,4‐dichlorophenoxyacetic acid (2,4‐D)), rather fast template rebinding kinetics, and appreciable selectivity over structurally related compounds. The binding association constant Ka and apparent maximum number Nmax for the high‐affinity sites of the 2,4‐D imprinted polymer were determined by Scatchard analysis and found to be 1.18 × 104 M−1 and 4.37 μmol/g, respectively. In addition, the general applicability of ILRPP in molecular imprinting was also confirmed by the successful preparation of MIP microspheres with another template (2‐chloromandelic acid). In particular, the living nature of ILRPP makes it highly useful for the facile one‐pot synthesis of functional polymer/MIP microspheres with surface‐bound iniferter groups, which allows their direct controlled surface modification via surface‐initiated iniferter polymerization and is thus of great potential in preparing advanced polymer/MIP materials. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3217–3228, 2010

Molecular Recognition Properties of Artemisinin - Imprinted Polymer Microspheres

The ability of molecularly-imprinted polymers (MIPs) to recognize and remember the shape of an imprinted molecule has expanded the application of these materials for separation and sample enrichment. This paper describes the binding efficiency and characteristics of an MIP prepared for the selective extraction of artemisinin, a potent anti-malaria compound present in Artemisia annua. Artemisinin is currently used in combination therapy for the treatment of severe cases of malaria.The MIP microspheres were obtained via precipitation polymerization using 5:6:20 mmol artemisinin/methacrylic acid/ethylene glycol dimethacrylate in 5% toluene/acetonitrile (95% v/v) solvent. This material showed high selectivity for artemisinin by rebinding experiments. Scatchard analysis was also carried out to further understand the binding characteristics of this material towards aremisinin.

Water Compatible Molecularly Imprinted Polymer Microspheres for Extraction of Ampicillin in Foods

The ampicillin (AMPI) molecularly imprinted polymer microspheres (MIPMs) via aqueous suspension polymerization were synthesized for the first time. Evaluation on the MIPMs by chromatographic analysis indicated that the optimum type and ratio of functional monomer to the template was 2-(Diethylamino) ethyl methacrylate (DEAEM) and 8:1, respectively. Under the optimized MISPE conditions, the recoveries were all above 89% for spiked AMPI in honey samples. After MISPE treatment, the obtained AMPI chromatograms showed that the matrix interferences could be almost neglected. The results demonstrate that the obtained MIPMs are applicable as inner adsorbents in MISPE cartridges for extraction of AMPI in foods.

Synthesis of nicotinamide-based molecularly imprinted microspheres and in vitro controlled release studies

Nicotinamide (NAM), which is one of the two principal forms, together with nicotinic acid, of vitamin B3, is both a food nutrient and a drug. Controlled NAM release systems are useful to extend the duration of the drug’s pharmacological activity and to minimize administration frequency. In this paper, molecularly imprinted polymers (MIPs) have been used as unconventional synthetic polymeric carriers, to prepare drug delivery systems for sustained release of NAM molecules. In the present study, various MIPs micro-spheres have been synthesized by using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Different stoichiometric ratios of the reagents have been used, in order to evaluate their influence on NAM recognition and release properties. Non-imprinted systems have been also been prepared as controls. MIPs binding capacity has been evaluated; NAM loading and in vitro release studies, in buffer solution (pH 7.2), that mimics blood plasma conditions, have been performed. Polymer P4 has given the best results since it enables it to rebind selectively and to prolong the release of NAM with higher performance than the non-imprinted one.

Synthesis and Characterization of Molecularly Imprinted Polymer Microspheres for Recognition of Chlorpyrifos

Synthesis and Characterization of Molecularly Imprinted Polymer Microspheres for Recognition of Chlorpyrifos

Improvement on Analyte Extraction by Molecularly Imprinted Polymer Microspheres toward Enrofloxacin

A collection of molecularly imprinted polymer microspheres (MIPMs) for Enrofloxacin (ENRO) were for the first time obtained through suspension polymerization in this work. The appropriate MIPMs used as specific SPE adsorbents were selected based on evaluation of binding capacities and morphology characterization. Combined with one simpler MISPE procedure for cleanup and preconcentration of ENRO in milk, further HPLC-UV analysis showed improved sensitivity of 10 µg kg−1 than those reported in previous studies, with the desirable recoveries of 73.6–101.6%, proving that the developed MIPMs are applicable for extraction of ENRO during the process of sample preparation.

Molecularly imprinted polymer based on chemiluminescence imaging for the chiral recognition of dansyl-phenylalanine

A new molecularly imprinted polymer (MIP)-chemiluminescence (CL) imaging detection approach towards chiral recognition of dansyl-phenylalanine (Phe) is presented. The polymer microspheres were synthesized using precipitation polymerization with dansyl-L-Phe as template. Polymer microspheres were immobilized in microtiter plates (96 wells) using poly(vinyl alcohol) (PVA) as glue. The analyte was selectively adsorbed on the MIP microspheres. After washing, the bound fraction was quantified based on peroxyoxalate chemiluminescence (PO-CL) analysis. In the presence of dansyl-Phe, bis(2,4,6-trichlorophenyl)oxalate (TCPO) reacted with hydrogen peroxide (H2O2) to emit chemiluminescence. The signal was detected and quantified with a highly sensitive cooled charge-coupled device (CCD). Influencing factors were investigated and optimized in detail. Control experiments using capillary electrophoresis showed that there was no significant difference between the proposed method and the control method at a confidence level of 95%. The method can perform 96 independent measurements simultaneously in 30 min and the limits of detection (LODs) for dansyl-L-Phe and dansyl-D-Phe were 0.025 micromol L(-1) and 0.075 micromol L(-1) (3sigma), respectively. The relative standard deviation (RSD) for 11 parallel measurements of dansyl-L-Phe (0.78 micromol L(-1)) was 8%. The results show that MIP-based CL imaging can become a useful analytical technology for quick chiral recognition.

Molecularly imprinted polymer microspheres for solid-phase extraction of chloramphenicol residues in foods

Preparation of molecularly imprinted polymer microspheres (MIPMs) for chloramphenicol (CAP) by aqueous suspension polymerization is reported for the first time in this study. The resulting MIPMs had the ability to specifically adsorb CAP, and the molecularly imprinted solid phase extraction (MISPE) based on the MIPMs was shown to be applicable for clean-up and preconcentration of trace CAP in milk and shrimp samples with high recoveries of 92.7% and 84.9%, respectively. Combined with MISPE, the conventional HPLC-UV analysis sensitivity for CAP in foods could be significantly increased.